1. Field:
This disclosure is concerned generally with the preparation of antibodies and specifically with the use of a virucidal agent in a process for precipitating antibodies from an antibody source that may include dangerous viruses.
2. Prior Art:
Antibodies are high molecular weight proteins that can be obtained from blood or more recently, from cultures of single cell lines (clones) that express monoclonal antibodies. The antibodies obtained from blood are commonly made by fractionating blood plasma using any of several processes such as one of the processes known as the Cohn process or a variation of it.
Antibodies are often classified as to type (IgG, IgM, IgA, etc.) and sometimes as to sub-type (IgGl, IgG2, IgG3, and IgG4). When obtained from plasma for therapeutic purposes, most antibodies prepared are of the IgG type (e.g. Gamimune.RTM., available from Miles Inc.; Gamagard.TM., available from Baxter International; Sandimune.TM., available from Sandoz; and Venoglobulin.TM., from Alpha Therapeutics. Although therapeutic IgM products are not common, at least one product comprising IgM enriched IgG is available in Europe from Biotest, Gmbh (Pentaglobin.TM.). It is believed the preparation of this product is described generally in U.S. Pat. No. 4,318,902, to Stephan.
More recently, the preparation of IgM--including therapeutic products has been described in U.S. patent application Ser. No. 83,136 in the name of G. Dove et al (primarily monoclonal IgM antibodies) and U.S. patent application Ser. No. 203,377 in the name of M.S. Collins et al (primarily plasma-derived IgM). See also patent application Ser. No. 504,161 in the name of G. C. Tsay et al (heat treated IgM preparations).
In preparing IgM enriched antibodies, it should be noted that there exists a potential, however remote, for the presence of viruses. While the source of such viruses can be either blood plasma or a monoclonal antibody cell culture, the potential for viral contamination is of special concern when the antibodies are derived from plasma using what is known as Cohn Fraction III. Fraction III, because of the processing steps that precede its generation, is a potential repository of blood-borne viruses that must be inactivated or removed for safety of a therapeutic IgM containing product.
While it is well known that IgG and IgM enriched products can be obtained (purified) from an aqueous solution by a process known as globulin or euglobulin precipitation, very little studies or prior art exist on assuring the inactivation of viruses in this process. Against this background, I have discovered a novel process for preparing an IgM-enriched IgG product that permits a relatively high IgM recovery while permitting a simultaneous viral inactivation step. Details of my process are described below.